The function of the kidney plasma membrane from alloxan-diabetic and normal rats will be compared using a number of enzyme and receptor activities as indices of membrane function. Enzymes intrinsic to the plasma membrane may be sensitive markers to reveal subtle structural alterations in the membrane. Classic plasma membrane marker enzymes to be assayed include 5'-nucleotidase, alkaline phosphatase, adenylate cyclase, and Na ion-K ion-ATPase. The last two activities are especially sensitive to regulatory influences and may therefore serve as sensitive indicators of membrane perturbations. Plasma membrane surface structures are also of interest. We will therefore study the peptide hormone binding sites known to exist on the kidney plasma membrane by measuring binding of parathyroid hormone, calcitonin, glucagon, and vasopressin. All hormone binding studies will be carried out under equilibrium conditions so that receptor affinities may be calculated and the receptor from diabetic and normal membrane compared quantitatively. In all studies we will correlate the enzyme and receptor data with physiological data on the individual animals used to prepare the plasma membranes. Observed biochemical alterations may be affected by the degree of hyperglycemia, ketosis, acidosis, lipid metabolism shifts, the duration of diabetes, or the dose of alloxan used to induce the disease. The above studies will be useful to evaluate the contribution of metabolic alterations to diabetic membrane pathology in an animal model resembling the juvenile diabetic. A second group of studies will be carried out in animals genetically predisposed to diabetes whose disease resembles adult onset diabetes. These studies will 1) determine whether the alterations observed in the alloxan-diabetic rat also occur in animal models more closely resembling adult onset diabetics, and 2) determine whether any of the observed changes occur in the pre-diabetic animal.